What are the effects of using any airway clearance technique compared to not using an airway clearance technique for clearing excess mucus from the lungs of people with cystic fibrosis?
The lungs of people with cystic fibrosis produce excess mucus. This leads to repeated infection and tissue damage in the lungs. It is important to clear the mucus using medicines and airway clearance techniques (physiotherapy). There are different airway clearance techniques for clearing mucus, some of which may include the use of mechanical devices. Daily physiotherapy takes a lot of time and trouble, so it is important to know if it works. We searched for studies where the people taking part had equal chances of being in the group using airway clearance techniques or the group with no airway clearance techniques. This is an update of a previously published review.
The evidence is current to 17 October 2022.
We included 12 studies that enrolled 194 people with cystic fibrosis. The studies were very different and some looked at multiple treatments compared to no treatment. One study used autogenic drainage (a controlled breathing technique which uses different speeds and depths of exhaled breath to move mucus up the airways so it can be cleared by coughing); five studies used conventional chest physiotherapy (manual techniques of percussion and vibration applied to the chest wall, usually with the assistance of a physiotherapist or relative); nine used positive expiratory pressure (breathing out through a mask or mouthpiece against a resistance which causes pressure to build up in the lungs to move the mucus), and one of these varied pressure so used both standard and high-pressure positive expiratory pressure; three studies used oscillating positive expiratory pressure (positive expiratory pressure combined with vibrations within the airway to loosen mucus); two used exercise (on a treadmill); and two used high-frequency chest wall oscillation (high frequency vibrations applied outside the chest wall via an inflatable garment). We could not combine any results to analyse them statistically.
Summarising the findings of the 12 studies, we found limited evidence of a short-term impact on lung function. Only one study reported an improvement in lung function in some of the treatment groups, whilst six other studies found no improvement.
This review found that methods of clearing the airways may have short-term benefits for moving mucus. Four studies found that the people using airway clearance techniques coughed up more sputum, but one study reported no difference with or without using an airway clearance technique. Five studies reported increased radioactive tracer clearance (a test in which people are imaged continuously after inhaling a radioaerosol to assess the time for it to be cleared from the lung) when using airway clearance, but one study of positive expiratory pressure found no difference. At present, there is no clear evidence to show the long-term effects of performing airway clearance techniques on quality of life or survival.
Limitations of the evidence
We have little or very little confidence in the evidence, for several reasons. Most included studies had design problems, and in just under half of the studies, it was unclear whether all the results were reported. Also, in physiotherapy studies, the person receiving treatment and their physiotherapist know which treatment they are receiving, and this may affect some of the findings. For example, the amount of mucus coughed up and lung function tests (measured by half of the included studies) and a person's views on a particular technique (recorded in a quarter of the included studies) may be affected if a person is aware of which treatment they are receiving. Finally, it was not clear in most studies whether the individual was experienced with the technique they were using.
We were unable to find any studies looking at the effects of airway clearance techniques in people treated with the new cystic fibrosis transmembrane conductance regulator (CFTR) modulator treatments. Cystic fibrosis is caused by faulty proteins on the cell surface made by the mutated CFTR gene; these new medicines are designed to correct the function of the faulty proteins.
The evidence from this review shows that ACTs may have short-term effects on increasing mucus transport in people with CF. All included studies had short-term follow-up; consequently, we were unable to draw any conclusions on the long-term effects of ACTs compared to no ACTs in people with CF.
The evidence in this review represents the use of airway clearance techniques in a CF population before widespread use of cystic fibrosis transmembrane conductance regulator (CFTR) modulators. Further research is needed to determine the effectiveness and acceptability of airway clearance in those treated with highly effective CFTR modulators.
Cystic fibrosis (CF) is an inherited progressive life-limiting disease characterised by the build-up of abnormally thick, sticky mucus affecting mostly the lungs, pancreas, and digestive system. Airway clearance techniques (ACTs), traditionally referred to as chest physiotherapy, are recommended as part of a complex treatment programme for people with CF. The aim of an ACTs is to enhance mucociliary clearance and remove viscous secretions from the airways within the lung to prevent distal airway obstruction. This reduces the infective burden and associated inflammatory effects on the airway epithelia.
There are a number of recognised ACTs, none of which have shown superiority in improving short-term outcomes related to mucus transport. This systematic review, which has been updated regularly since it was first published in 2000, considers the efficacy of ACTs compared to not performing any ACT in adults and children with CF. It is important to continue to review this evidence, particularly the long-term outcomes, given the recent introduction of highly effective modulator therapies and the improved health outcomes and potential changes to CF management associated with these drugs.
To determine the effectiveness and acceptability of airway clearance techniques compared to no airway clearance techniques or cough alone in people with cystic fibrosis.
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings, to 17 October 2022. We searched ongoing trials registers (Clinicaltrials.gov and the WHO International Clinical Trials Registry Platform) to 7 November 2022.
We included randomised or quasi-randomised studies that compared airway clearance techniques (chest physiotherapy) with no airway clearance techniques or spontaneous cough alone in people with CF.
Both review authors independently assessed study eligibility, extracted data, and assessed the risk of bias of the included studies. We used GRADE methodology to assess the certainty of the evidence.
We included 11 cross-over studies (153 participants) and one parallel study (41 participants). There were differences between studies in how the interventions were delivered, with several intervention groups combining more than one ACT. One study used autogenic drainage; five used conventional chest physiotherapy; nine used positive expiratory pressure (PEP), with one study varying the water pressure between arms; three studies used oscillating PEP; two used exercise; and two used high-frequency chest wall oscillation (HFCWO). Of the 12 included studies, 10 were single-treatment studies, and two delivered the intervention over two consecutive days (once daily in one study, twice daily in the second). This substantial heterogeneity in the treatment interventions precluded pooling of data for meta-analysis. Blinding of participants, caregivers, and clinicians is impossible in airway clearance studies; we therefore judged all studies at unclear risk of performance bias. Lack of information in eight studies made assessment of risk of bias unclear for most other domains.
We rated the certainty of evidence as low or very low due to the short-term cross-over trial design, small numbers of participants, and uncertain risk of bias across most or all domains.
Six studies (84 participants) reported no effect on pulmonary function variables following intervention; but one study (14 participants) reported an improvement in pulmonary function following the intervention in some of the treatment groups. Two studies reported lung clearance index: one (41 participants) found a variable response to treatment with HFCWO, whilst another (15 participants) found no effect on lung clearance index with PEP therapy (low-certainty evidence). Five studies (55 participants) reported that ACTs, including coughing, increased radioactive tracer clearance compared to control, while a further study (eight participants) reported no improvement in radioactive tracer clearance when comparing PEP to control, although coughing was discouraged during the PEP intervention. We rated the certainty of evidence on the effect of ACTs on radioactive tracer clearance as very low.
Four studies (46 participants) investigated the weight of mucus cleared from the lungs and reported greater secretions during chest physiotherapy compared to a control. One study (18 participants) reported no differences in sputum weight (very low-certainty evidence).